Meloxicam, a COX-2 Inhibitor, Ameliorates Ischemia/Reperfusion Injury in Non-Heart-Beating Donor Livers

Abstract

Background/Aims: Chronic organ donor shortage has led to the consideration to expand the donor pool with livers from non-heart-beating donors (NHBD), although a higher risk of graft dys- or nonfunction is associated with these livers. We examined the effects of selective cyclooxygenase-2 (COX-2) inhibition on hepatic warm ischemia (WI) reperfusion (I/R) injury of NHBD. Methods: Male Wistar rats were used as donors and meloxicam (5 mg/kg body weight) was administered into the preservation solution. Livers were excised after 60 min of WI in situ, flushed and preserved for 24 h at 4°C. Reperfusion was carried out in vitro at a constant flow for 45 min. During reperfusion (5, 15, 30 and 45 min), enzyme release of alanine aminotransferase and glutamate lactate dehydrogenase were measured as well as portal venous pressure, bile production and oxygen consumption. The production of malondialdehyde was quantified and TUNEL staining was performed. Quantitative PCR analyzed COX-2 mRNA. COX-2 immunohistochemistry and TxB₂ detection completed the measurements. Results: Meloxicam treatment led to better functional recovery concerning liver enzyme release, vascular resistance and metabolic activity over time in all animals. Oxidative stress and apoptosis were considerably reduced. Conclusion: Cold storage using meloxicam resulted in significantly better integrity and function of livers retrieved from NHBD. Selective COX-2 inhibition is a new therapeutic approach achieving improved preservation of grafts from NHBD.